Shi G P, Webb A C, Foster K E, Knoll J H, Lemere C A, Munger J S, Chapman H A
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115.
J Biol Chem. 1994 Apr 15;269(15):11530-6.
The human lysosomal cysteine proteinases, cathepsins H, L, and B, have been mapped to chromosomes 15, 9, and 8, respectively, and the genomic structures of cathepsins L and B have been determined. We report here the chromosomal localization and partial gene structure for a recently sequenced human cysteine proteinase, cathepsin S. A 20-kilobase pair genomic clone of the human cathepsin S gene was isolated from a human fibroblast genomic library and used to map the human cathepsin S gene to chromosome 1q21 by fluorescence in situ hybridization. This clone contains exons 1 through 5, introns 1 through 4, part of intron 5, and > 7 kilobase pairs of the 5'-flanking sequence. The gene structure of human cathepsin S is similar to that of cathepsin L through the first 5 exons, except that cathepsin S introns are substantially larger. Sequencing of the 5'-flanking region revealed, similar to human cathepsin B, no classical TATA or CAAT box. In contrast to cathepsin B, cathepsin S contains only two SP1 and at least 18 AP1 binding sites that potentially could be involved in regulation of the gene. This 5'-flanking region also contains CA microsatellites. The presence of AP1 sites and CA microsatellites suggest that cathepsin S can be specifically regulated. Results of Northern blotting using probes for human cathepsins B, L, and S are consistent with this hypothesis; only cathepsin S shows a restricted tissue distribution, with highest levels in spleen, heart, and lung. In addition, immunostaining of lung tissue demonstrated detectable cathepsin S only in lung macrophages. The high level of expression in the spleen and in phagocytes suggests that cathepsin S may have a specific function in immunity, perhaps related to antigen processing.
人类溶酶体半胱氨酸蛋白酶组织蛋白酶H、L和B分别定位于15号、9号和8号染色体，并且已经确定了组织蛋白酶L和B的基因组结构。我们在此报告一种最近测序的人类半胱氨酸蛋白酶——组织蛋白酶S的染色体定位和部分基因结构。从人类成纤维细胞基因组文库中分离出人类组织蛋白酶S基因的一个20千碱基对的基因组克隆，并通过荧光原位杂交将人类组织蛋白酶S基因定位于1号染色体长臂2区1带。该克隆包含第1至5外显子、第1至4内含子、第5内含子的一部分以及超过7千碱基对的5'侧翼序列。人类组织蛋白酶S的基因结构在前5个外显子上与组织蛋白酶L相似，只是组织蛋白酶S的内含子要大得多。对5'侧翼区域的测序显示，与人类组织蛋白酶B相似，没有典型的TATA盒或CAAT盒。与组织蛋白酶B不同，组织蛋白酶S仅含有两个SP1和至少18个AP1结合位点，这些位点可能参与该基因的调控。这个5'侧翼区域还包含CA微卫星。AP1位点和CA微卫星的存在表明组织蛋白酶S可以受到特异性调控。使用针对人类组织蛋白酶B、L和S的探针进行的Northern印迹分析结果与这一假设一致；只有组织蛋白酶S显示出有限的组织分布，在脾脏、心脏和肺中水平最高。此外，肺组织的免疫染色显示仅在肺巨噬细胞中可检测到组织蛋白酶S。在脾脏和吞噬细胞中的高表达水平表明组织蛋白酶S可能在免疫中具有特定功能，也许与抗原加工有关。
